Yoon H H, Bendell J C, Braiteh F S, Firdaus I, Philip P A, Cohn A L, Lewis N, Anderson D M, Arrowsmith E, Schwartz J D, Gao L, Hsu Y, Xu Y, Ferry D, Alberts S R, Wainberg Z A
Medical Oncology, Mayo Clinic, Rochester, MN
GI Cancer Research Program, Sarah Cannon Research Institute, Tennessee Oncology, Nashville.
Ann Oncol. 2016 Dec;27(12):2196-2203. doi: 10.1093/annonc/mdw423. Epub 2016 Oct 20.
We report the first randomized, Phase II trial of ramucirumab, an anti-vascular endothelial growth factor receptor-2 monoclonal antibody, as front-line therapy in patients with advanced adenocarcinoma of the esophagus or gastric/gastroesophageal junction (GEJ).
Patients from the USA with advanced esophageal, gastric, or GEJ adenocarcinoma randomly received (1:1) mFOLFOX6 plus ramucirumab (8 mg/kg) or mFOLFOX6 plus placebo every 2 weeks. The primary end point was progression-free survival (PFS) with 80% power to detect a hazard ratio (HR) of 0.71 (one-sided α = 0.15). Secondary end points included evaluation of response and overall survival (OS); an exploratory ramucirumab exposure-response analysis was undertaken.
Of 168 randomized patients, 52% of tumors were located in the stomach/GEJ and 48% in the esophagus. The trial did not meet the primary end point of PFS [6.4 versus 6.7 months, HR 0.98 (95% confidence interval 0.69-1.37)] or the secondary end point of OS (11.7 versus 11.5 months) in the intent-to-treat (ITT) population. Objective response rates (45.2% versus 46.4%) were similar between arms. Most Grade ≥3 toxicities did not differ significantly between arms, yet premature discontinuation of FOLFOX and ramucirumab (for reasons other than progressive disease) was more common among ramucirumab- versus placebo-treated patients. In an exploratory analysis that censored for premature discontinuation, the HR for PFS favored the ramucirumab arm (HR 0.76), particularly in patients with gastric/GEJ cancer. An exploratory exposure-response analysis indicated that patients with higher ramucirumab exposure had longer OS.
The addition of ramucirumab to front-line mFOLFOX6 did not improve PFS in the ITT population.
NCT01246960.
我们报告了一项关于雷莫西尤单抗（一种抗血管内皮生长因子受体-2单克隆抗体）作为晚期食管癌或胃/胃食管交界（GEJ）腺癌患者一线治疗的首个随机II期试验。
来自美国的晚期食管、胃或GEJ腺癌患者每2周随机接受（1:1）mFOLFOX6加雷莫西尤单抗（8mg/kg）或mFOLFOX6加安慰剂治疗。主要终点是无进展生存期（PFS），检测风险比（HR）为0.71的效能为80%（单侧α=0.15）。次要终点包括疗效评估和总生存期（OS）；进行了一项探索性雷莫西尤单抗暴露-反应分析。
168例随机分组患者中，52%的肿瘤位于胃/GEJ，48%位于食管。在意向性治疗（ITT）人群中，该试验未达到PFS的主要终点[6.4个月对6.7个月，HR 0.98（95%置信区间0.69-1.37）]或OS的次要终点（11.7个月对11.5个月）。两组的客观缓解率相似（45.2%对46.4%）。大多数≥3级毒性在两组之间无显著差异，但在接受雷莫西尤单抗治疗的患者中，因FOLFOX和雷莫西尤单抗过早停药（因疾病进展以外的原因）比接受安慰剂治疗患者更常见。在一项针对过早停药进行 censored 的探索性分析中，PFS的HR有利于雷莫西尤单抗组（HR 0.76），尤其是在胃/GEJ癌患者中。一项探索性暴露-反应分析表明，雷莫西尤单抗暴露量较高的患者OS更长。
在一线mFOLFOX6基础上加用雷莫西尤单抗未改善ITT人群的PFS。
NCT012⒋6960。
